The principal objective of this research grant is to understand the mechanisms of change in lipid, particularly phospholipid, composition of the arterial wall during the course of atherogenesis in squirrel monkeys or aging in rhesus monkeys. We will study the mechanism of increase in arterial lysolecithin and sphingomyelin concentrations in a variety of in vivo and in vitro preparations. The metabolism of lipoprotein proteins and phospholipids and their exchange with and net flow to arterial tissue will be investigated in squirrel monkeys. Since we have shown that these monkeys also develop gallstones on many of our semipurified diets, we will investigate the relationships of diet and one drug (chenodeoxycholic acid), of plasma and of arterial lipids to the incidence of gallstones and certain aspects of biliary metabolism. These factors in biliary metabolism include composition of hepatic and gallbladder bile, bile acid pool sizes and fractional turnover rates, and the effects of interruption of the enterohepatic circulation. We propose to study the morphology of these gallstones and certain intermediary forms. We are also investigating the relationship of phospholipid and cerebroside metabolism as an index of myelination in different parts of the rhesus monkey brain during development.